Concomitants of alcoholism: differential effects of thiamine deficiency, liver damage, and food deprivation on the rat brain in vivo

Abstract

Rationale Serious neurological concomitants of alcoholism include Wernicke's Encephalopathy (WE), Korsakoff's Syndrome (KS) and hepatic encephalopathy (HE). Objectives This study was conducted in animal models to determine neuroradiological signatures associated with liver damage caused by carbon tetrachloride (CCl4), thiamine deficiency caused by pyrithiamine treatment, and nonspecific nutritional deficiency caused by food deprivation. Methods Magnetic resonance imaging (MRI) and spectroscopy (MRS) were used to evaluate brains of wild-type Wistar rats at baseline and following treatment. Results Similar to observations in ethanol (EtOH) exposure models, thiamine deficiency caused enlargement of the lateral ventricles. Liver damage was not associated with effects on cerebrospinal fluid volumes, whereas food deprivation caused modest enlargement of the cisterns. In contrast to what has repeatedly been shown in EtOH exposure models, in which levels of choline-containing compounds (Cho) measured by MRS are elevated, Cho levels in treated animals in all 3 experiments (i.e., liver damage, thiamine deficiency, food deprivation) were lower than baseline or controls. Conclusions These results add to the growing body of literature suggesting that MRS-detectable Cho is labile and can depend on a number of variables that are not often considered in human experiments. These results also suggest that reductions in Cho observed in humans with alcohol use disorder (AUD) may well be due to mild manifestations of concomitants of AUD such as liver damage or nutritional deficiencies and not necessarily to alcohol consumption per se.

Cigarette smoking history is associated with poorer recovery in multiple neurocognitive domains following treatment for an alcohol use disorder

“…Given that chronic smoking is associated with multiple neurobiological abnormalities in "healthy" non-AUD samples (Durazzo et al, 2014b;Durazzo et al, 2016;Durazzo, Meyerhoff, & Murray, 2015;Durazzo, Meyerhoff, & Yoder, 2018;Durazzo, Meyerhoff, Yoder, & Murray, 2017;Duriez, Crivello, & Mazoyer, 2014;Franklin et al, 2014;Fritz et al, 2014;Gallinat & Schubert, 2007;Gons et al, 2011;Hanlon et al, 2016;Kuhn et al, 2012;Schubert, Seifert, Bajbouj, & Gallinat, 2006;Stoeckel, Chai, Zhang, Whitfield-Gabrieli, & Evins, 2016;Sutherland et al, 2016;Zanchi et al, 2015), nvsALC may possess greater neurobiological and neurocognitive resiliency to the adverse consequences of AUD, compared to fsALC and asALC. In addition to chronic cigarette smoking, it is possible that premorbid factors (e.g., genetic risk or resiliency factors), or comorbid factors not assessed in this study [e.g., diet/nutrition, exercise, and subclinical hepatic, pulmonary, cardiac, or cerebrovascular dysfunction (Durazzo, Hutchison, Fryer, Mon, & Meyerhoff, 2012;Fama et al, 2019;Hoefer et al, 2014;Mon et al, 2013;Tessner & Hill, 2010;Zahr, Kaufman, & Harper, 2011;Zahr et al, 2016)] influenced neurocognition in this ALC cohort. Any neurocognitive and neurobiological abnormalities observed in those with AUD following detoxification or after an extended period of abstinence are related to multiple premorbid and/or concurrent biopsychosocial factors, and not solely attributable to chronic and excessive alcohol consumption.…”

Jacobian Maps Reveal Under-reported Brain Regions Sensitive to Extreme Binge Ethanol Intoxication in the Rat

“…A voxel-based approach identified significant changes in response to binge EtOH treatment throughout the rat brain that parallel regions identified in human alcoholism (e.g., Zahr et al, 2011a; Zahr, 2014; Zahr and Pfefferbaum, 2017; Sullivan et al, 2018). In particular, the thalamus and colliculi feature significantly in the literature on Korsakoff syndrome and Wernicke's encephalopathy (Sullivan and Pfefferbaum, 2009; Jung et al, 2012), sequelae of chronic alcoholism attributable to dietary depletion of thiamine (Zahr et al, 2011a,b).…”

Jacobian Mapping Reveals Converging Brain Substrates of Disruption and Repair in Response to Ethanol Exposure and Abstinence in 2 Strains of Rats

“…These regions are also among those typically affected in Wernicke‐Korsakoff syndrome (WKS)—associated with thiamine deficiency—which has a characteristic and irreversible neuropathological pattern that includes damage to diencephalic structures (thalamus, hypothalamus, mammillary bodies), periaqueductal gray matter, anterior cerebellar vermis, and the quadrigeminal plate (i.e., corpora quadrigemina, tectum, including superior and inferior colliculi; e.g., Jung et al, 2012; Victor et al, 1971). Animal models of WKS using the thiamine antagonist pyrithiamine recapitulate human findings frequently demonstrating irreversible damage to mammillary nuclei, periaqueductal gray, and inferior colliculi; damage to regions including the hippocampus, thalamus, and cerebellum is also observed but less consistently (e.g., Pfefferbaum et al, 2007; Zahr et al, 2016b).…”